Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, United States of America.
Department of Biology, Division of Natural and Physical Sciences, Blinn College, Bryan, Texas, United States of America.
PLoS One. 2022 Oct 25;17(10):e0276744. doi: 10.1371/journal.pone.0276744. eCollection 2022.
Peptide Lv is a small endogenous secretory peptide that is expressed in various tissues and conserved across different species. Patients with diabetic retinopathy, an ocular disease with pathological angiogenesis, have upregulated peptide Lv in their retinas. The pro-angiogenic activity of peptide Lv is in part through promoting vascular endothelial cell (EC) proliferation, migration, and sprouting, but its molecular mechanism is not completely understood. This study aimed to decipher how peptide Lv promotes EC-dependent angiogenesis by using patch-clamp electrophysiological recordings, Western immunoblotting, quantitative PCR, and cell proliferation assays in cultured ECs. Endothelial cells treated with peptide Lv became significantly hyperpolarized, an essential step for EC activation. Treatment with peptide Lv augmented the expression and current densities of the intermediate-conductance calcium-dependent potassium (KCa3.1) channels that contribute to EC hyperpolarization but did not augment other potassium channels. Blocking KCa3.1 attenuated peptide Lv-elicited EC proliferation. These results indicate that peptide Lv-stimulated increases of functional KCa3.1 in ECs contributes to EC activation and EC-dependent angiogenesis.
肽 Lv 是一种小的内源性分泌肽，在各种组织中表达，并在不同物种中保守。患有糖尿病性视网膜病变（一种病理性血管生成的眼部疾病）的患者，其视网膜中上调了肽 Lv。肽 Lv 的促血管生成活性部分是通过促进血管内皮细胞（EC）增殖、迁移和发芽来实现的，但它的分子机制尚不完全清楚。本研究旨在通过在培养的 EC 中使用膜片钳电生理记录、Western 免疫印迹、定量 PCR 和细胞增殖测定来破译肽 Lv 如何促进 EC 依赖性血管生成。用肽 Lv 处理的内皮细胞变得明显超极化，这是 EC 激活的必要步骤。肽 Lv 的处理增强了对 EC 超极化有贡献的中电导钙依赖性钾（KCa3.1）通道的表达和电流密度，但没有增强其他钾通道。阻断 KCa3.1 可减弱肽 Lv 诱导的 EC 增殖。这些结果表明，肽 Lv 刺激 EC 中功能性 KCa3.1 的增加有助于 EC 激活和 EC 依赖性血管生成。
